The Crucial Consortium aims to address a difficult problem regarding how co-morbidities give rise both to mental disorders and non-mental disorders. In order to achieve this, they have assembled a consortium that has a balanced mix of skills on several levels.

It consists of fundamental scientists and clinicians. It consists of specialists in neuroscience (UM, Scannexus) and in cardiovascular science (UCL, UNAV, FIMA, GlycoCheck, KU Leuven, VIB).

The clinical scientists are strong leaders in the field of MRI (UCL, UM, UNAV, Scannexus), whereas the fundamental partners have strong skills in molecular biology and genetics that will allow them to develop new biomarkers and identify new pathways for pharmaceutical targeting (FIMA, KU Leuven, VIB). Beyond bridging fundamental research and clinical applications, the project also combines several state-of-the-art technical approaches to answer the research objective. This includes cell signalling, (single cell) RNA-Seq, metabolic assessments, microvesicle’s biomarker identification, GlycoCheck measurements, and advanced imaging (MRI, 2-photon and light sheet microscopy). Read more here.

Objective:
To investigate whether intervention with the dietary supplement Endocalyx™ improves the
Microvascular Health Index between baseline and 3 months in type 2 diabetic South Asian patients with
microalbuminuria in comparison to the placebo group.

Daniel Machin and Tony Donato published an abstract at the Experimental Biology 2019 meeting on the effect of Endocalyx on aging in mice:

Published in The FASEB Journal (volume 33, Issue 1_supplement, 01 April 2019):

Published Online: 1 Apr 2019 Abstract Number: 828.1

Abstract

Large elastic artery stiffening and endothelial dysfunction, and associated reductions in nitric oxide (NO) bioavailability, are central features of vascular aging. We have recently demonstrated that the glycocalyx, a gel-like structure that is bound to the luminal surface of the vascular endothelium, is dysfunctional in the aged vasculature. The glycocalyx has several functions that are critical for the maintenance of a healthy vasculature. We sought to determine if chronic dietary supplementation of glycocalyx precursors (glucosamine sulfate, fucoidan, superoxide dismutase, and high molecular weight hyaluronan) could restore glycocalyx function, while concomitantly ameliorating age-related vascular dysfunction. Young (Y: 7 mo) and old (O: 30 mo) male B6D2F1 mice consumed a control (C) or glycocalyx precursor (GP: 37 mg/kg encapsulated chow provided courtesy of MicroVascular Health Solutions, LLC [U.S. Patent Serial No. 9,943,572]) diet ad libitum for 10 weeks. Glycocalyx barrier function (perfused boundary region [PBR]) was evaluated in the mesenteric microcirculation using an intravital microscope equipped with an automated capture and analysis system. PBR was ~13% higher in OC compared to YC, suggestive of an age-related impairment in glycocalyx barrier function, and this was normalized in OGP mice (Both P<0.05; Figure 1). At baseline, aortic pulse wave velocity (PWV), a measure of large artery stiffness, was higher in OC and OGP compared with YC mice (Both P<0.05; Figure 2). However, after the dietary intervention, PWV decreased by ~13% in OGP (P<0.05), whereas, PWV was unchanged in OC and YC mice after the 10 week period (P>0.05). We assessed endothelial function by endothelium-dependent dilation (EDD, maximal response to acetylcholine [ACh]) in the carotid artery. Carotid artery EDD was higher in YC and OGP compared to OC mice (92.5±2.4 and 90.7±2.3 vs. 69.0±4.9%, respectively, P<0.05). EDD of OGP was similar to YC mice (P>0.05). After incubation with the nitric oxide (NO) synthase inhibitor, L-NAME, the dilatory response did not differ between groups (P>0.05). NO bioavailability (max ACh dilation - max ACh+L-NAME dilation) was ~10–14 fold higher in YC and OGP compared to OC mice (Both P<0.05; Figure 3). Endothelium-independent dilation (vasodilation to sodium nitroprusside) was not different between groups (P>0.05). In young mice, GP diet did not affect any of the aforementioned measurements (P>0.05). In conclusion, 10 weeks of dietary GP supplementation in old mice restores glycocalyx barrier function that is accompanied by reduced aortic stiffness and augmented EDD and NO bioavailability, suggesting that the glycocalyx may be an effective therapeutic target for vascular dysfunction in older adults.

Support or Funding Information

This study was funded in part by grants from the National Institute of Health (R01 AG040297, R01 AG048366, K02 AG045339, K99 AT010017) and US Department of Veterans Affairs (1I01BX002151).

Pilot Study in 13 Healthy Volunteers

Summary of Findings from Clinical Studies

6.3.2 Food supplement
A pilot study was conducted among 13 healthy volunteers receiving the Endocalyx food supplement. After 3 months, the Microvascular Health Index measured by SDF imaging improved by 31%. After 4 months, the Microvascular Health Index in the volunteers improved by 50%. This showed the beneficial effects of the food supplement on the microvasculature as it significantly increased capillary density and red blood cell filling percentage, and reduced the perfused boundary region (unpublished data, H. Vink).

Summary of Known and Potential Risks and Benefits

6.4.2 Food supplement
In the pilot study with Endocalyx, no serious adverse effects were reported. One side effect that was reported was dizziness, as the Endocalyx supplement lowered the systolic blood pressure. The supplement is already used in general practitioners’ offices in the United States and to date; no one reported any major side effects. Studies conducted with the individual ingredients also did not report any serious adverse effects. A possible side effect may be an unknown allergic reaction to one of the ingredients of the supplement. Benefits of the Endocalyx food supplement in diabetic patients remain to be established but are mainly improving the microvascular health by supporting endothelial glycocalyx function.